2y8b

VIM-7 with Oxidised. Structural and computational investigations of VIM-7: Insights into the substrate specificity of VIM metallo-beta- lactamases

spinqualitylabelsall models 2y8b, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y8b is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: OCS, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLBV7_PSEAI Class B beta-lactamase which confers resistance to the beta-lactam antibiotics, including penicillins, cephalosporins and carbapenems (PubMed:14693560). Acts via hydrolysis of the beta-lactam ring (PubMed:18559652). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities (PubMed:18559652). Publication Abstract from PubMed The presence of metallo-beta-lactamases (MBLs) in many clinically important human bacterial pathogens limits treatment options, as these enzymes efficiently hydrolyze nearly all beta-lactam antibiotics. VIM enzymes are among the most widely distributed MBLs, but many of the individual VIM subtypes remain poorly characterized. Pseudomonas aeruginosa VIM-7 is the most divergent among VIM-type MBLs in terms of amino acid sequence. Here we present crystal structures of VIM-7 as the native enzyme, with Cys221 oxidized (VIM-7-Ox), and with a sulfur atom bridging the two active-site zinc ions (VIM-7-S). Comparison with VIM-2 and VIM-4 structures suggests an explanation for the reduced catalytic efficiency of VIM-7 against cephalosporins with a positively charged cyclic substituent at the C3 position (e.g., ceftazidime). Kinetic variations are attributed to substitutions in residues 60-66 (that form a loop adjacent to the active site previously implicated in substrate binding) and to the disruption of two hydrogen-bonding clusters through substitutions at positions 218 and 224. Furthermore, the less negatively charged surface of VIM-7 (compared to VIM-2) may also contribute to the reduced hydrolytic efficiency. Docking of the cephalosporins ceftazidime and cefotaxime into the VIM-2 and VIM-7 structures reveals that amino acid substitutions may cause the mode of substrate binding to differ between the two enzymes. Our structures thus provide new insights into the variation in substrate specificity that is evident across this family of clinically important enzymes. Structural and Computational Investigations of VIM-7: Insights into the Substrate Specificity of VIM Metallo-beta-Lactamases.,Borra PS, Leiros HK, Ahmad R, Spencer J, Leiros I, Walsh TR, Sundsfjord A, Samuelsen O J Mol Biol. 2011 May 30. PMID:21645522 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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